Biomedical subjects

S-T Yau

Publications and source records attributed to S-T Yau.

2 recordsLinked to original sources

PubMed2004

Crystallization mechanisms of hemoglobin C in the R state.

Crystallization of the mutated hemoglobin, HbC, which occurs inside red blood cells of patients expressing betaC-globin and exhibiting the homozygous CC and the heterozygous SC (in which two mutant beta-globins, S and C, are expressed) diseases, is a convenient model for processes underlying numerous condensation diseases. As a first step, we investigated the molecular-level mechanisms of crystallization of this protein from high-concentration phosphate buffer in its stable carbomonoxy form using high-resolution atomic force microscopy. We found that in conditions of equilibrium with the solution, the crystals' surface reconstructs into four-molecule-wide strands along the crystallographic a (or b) axis. However, the crystals do not grow by the alignment of such preformed strands. We found that the crystals grow by the attachment of single molecules to suitable sites on the surface. These sites are located along the edges of new layers generated by two-dimensional nucleation or by screw dislocations. During growth, the steps propagate with random velocities, with the mean being an increasing function of the crystallization driving force. These results show that the crystallization mechanisms of HbC are similar to those found for other proteins. Therefore, strategies developed to control protein crystallization in vitro may be applicable to pathology-related crystallization systems.

Crystallization↗

PubMed2003

Dissipating step bunches during crystallization under transport control.

In studies of crystal formation by the generation and spreading of layers, equidistant step trains are considered unstable-bunches and other spatiotemporal patterns of the growth steps are viewed as ubiquitous. We provide an example to the opposite. We monitor the spatiotemporal dynamics of steps and the resulting step patterns during crystallization of the proteins ferritin and apoferritin using the atomic force microscope. The variations in step velocity and density are not correlated, indicating the lack of a long-range attraction between the steps. We show that (i) because of its coupling to bulk transport, nucleation of new layers is chaotic and occurs at the facet edges, where the interfacial supersaturation is higher; (ii) step bunches self-organize via the competition for supply from the solution; and, (iii) bunches of weakly interacting steps decay as they move along the face. Tests by numerical modeling support the conclusions about the mechanisms underlying our observations. The results from these systems suggest that during crystallization controlled by transport, with weakly or noninteracting growth steps, the stable kinetic state of the surface is an equidistant step train, and step bunches only arise during nucleation of new layers. Since nucleation only occurs at a few sites on the surface, the surface morphology may be controllably patterned or smoothened by locally controlling nucleation.

Journal Article↗